Journal
CHEMBIOCHEM
Volume 14, Issue 13, Pages 1581-1589Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/cbic.201300289
Keywords
alpha-pyrone antibiotics; biosynthesis; Myxcoccus fulvus; myxobacteria; polyketides
Funding
- German Centre for Infection Research (DZIF) partner site Hannover-Braunschweig
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Myxopyronins and corallopyronins are structurally related -pyrone antibiotics from myxobacteria. They are thought to represent a highly promising compound class for the development of broad-spectrum antibacterial therapeutic agents, because of their ability to inhibit RNA polymerase through interaction with the switch region, a recently identified novel drug target. Here we describe the identification and characterization of the myxopyronin biosynthetic pathway from Myxococcus fulvus Mx f50. A detailed comparison with the recently identified corallopyronin biosynthetic pathway revealed the genetic and biochemical basis, thus explaining the observed structural differences between the two natural product families. Directed mutagenesis procedures for M. fulvus Mx f50 were developed to enable functional studies and pathway modifications. Our work provided new insights into myxopyronin biosynthesis and led to the production of a novel and unexpected myxopyronin derivative.
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